Differential regulation of expression of three transforming growth factor beta species in human breast cancer cell lines by estradiol.
Transforming growth factor (TGF)-beta is a potent regulator of many cell functions and a growth inhibitor for mammary epithelial cells. We now know of three highly homologous members of the human TGF-beta gene family. We have studied the expression of TGF-beta 1, -beta 2, and -beta 3 mRNA in four human breast cancer cell lines. Using the RNase protection assay, we have detected mRNA expression of TGF-beta 1, -beta 2, and -beta 3 by T-47D cells, TGF-beta 1 and -beta 3 by ZR-75-1 cells, and TGF-beta 1 by MCF-7 cells. Treatment of these estrogen receptor-positive cells with 10 nM estradiol for 48 h resulted in decreased mRNA levels of TGF-beta 2 and -beta 3 but did not affect mRNA levels of TGF-beta 1. Expression of TGF-beta 1 and -beta 2 mRNA by an estrogen receptor-negative cell line, MDA-MB-231, was not changed by estradiol treatment. Treatment of cells with the antiestrogen tamoxifen (1 microM) did not significantly alter mRNA levels for any of the three TGF-beta species. We have further determined that estradiol treatment of T-47D was associated with diminished secretion of TGF-beta into the medium. Both TGF-beta 1 and -beta 2 inhibited the proliferation of MCF-7 cells, and neither protein affected the growth of T-47D cells. TGF-beta 1 was at least 10-fold more potent than TGF-beta 2 at inhibiting the growth of MCF-7 cells.
Arrick
B A
BA
Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Korc
M
M
Derynck
R
R
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D013629:Tamoxifen; D004958:Estradiol; D015291:Transforming Growth Factors